It is the primary objective of this research program to determine the cause of photoreceptor degeneration in the inherited diseases of rd mice and RCS rats. A systematic investigation of cyclic nucleotide metabolism is in progress. Using standard biochemical procedures, the enzymes of cyclic nucleotide metabolism and factors which control the intracellular concentration of cyclic AMP and cyclic GMP are being studied. This approach necessitates the purification of enzymes and their localization in situ, by immunocytochemical techniques. Cyclic nucleotides modulate enzyme phosphorylation and phosphoproteins of diseased photoreceptor cells will be investigated. Eye rudiments of Xenopus laevis will be cultured with appropriate drugs in order to simulate in normal retinas an inherited disease and the simulated disease will be investigated in terms of cyclic nucleotide metabolism. Our long-term aim is to develop a therapy for preventing visual cell degeneration in the drug-induced degenerative eye rudiments of Xenopus and to generalize this therapy for use in the rodent disorders.